Systematic review of safety and efficacy of therapeutic endoscopic-retrograde-cholangiopancreatography during pregnancy including studies of radiation-free therapeutic endoscopic-retrograde-cholangiopancreatography

Table 1 General principles of endoscopic retrograde cholangiopancreatography during pregnancy

1. Counsel patient, husband, and family on risks vs benefits of ERCP for mother as well as fetus

2. Obtain written informed consent from pregnant patient (not the father)

3. Endoscopist should assess whether his/her experience and skill is adequate for dealing with anticipated biliary pathology in a pregnant patient with this medical history

4. Position patient on left side or supine, if possible, especially during advanced pregnancy

5. Preferentially perform ERCP during second trimester, if possible

6. During late third trimester, delay elective ERCP to after delivery

7. Use safety guidelines (see Table 2) to minimize fetal radiation exposure and risks

8. Consider performing EUS prior to ERCP to assess CBD diameter as well as number, size, and shape of gallstones

9. Multidisciplinary input involving a perinatologist, high-risk obstetrician, obstetric anesthesiologist, radiation safety officer, and surgeon prior to ERCP

10. Administer parenteral fluids consistent with clinical status and pregnancy requirements

11. Reverse metabolic derangements and appropriately intervene to correct abnormalities in vital signs before scheduling ERCP

12. Administer antibiotics and other drugs during ERCP that are considered relatively safe during pregnancy

13. Endoscopist should be familiar with and prepared to use full armamentarium of endoscopic techniques including needle-knife sphincterotomy, transeptal sphincterotomy, choledochoscopy, and IDUS

14. Counsel patients regarding requirements for follow-up visits, especially with stent placement

15. Avoid pancreatic endotherapy during ERCP because this entails a higher risk than biliary endotherapy

ERCP: Endoscopic retrograde cholangiopancreatography; EUS: Endoscopic ultrasound; CBD: Common bile duct; IDUS: Intraductal ultrasound.

Table 2 Maximizing radiation safety of endoscopic retrograde cholangiopancreatography during pregnancy

1. Highly qualified and experienced ERCP endoscopist

2. Limited (solely observational) role of inexperienced gastroenterology fellow during ERCP

3. Informed consent to include discussion of radiation teratogenicity

4. Consult perinatologist

5. Consult radiation safety officer and medical physicist, if available, to minimize fetal radiation exposure

6. Endoscopist performing ERCP should become familiar with fluoroscopy equipment, especially with options to minimize radiation exposure

7. Formal consultation of anesthesiologist before ERCP

8. Anesthesiologist to attend during entire ERCP, even if nurse-anesthetist is present

9. Consider using an obstetric anesthesiologist rather than a general anesthesiologist for ERCP

10. Avoid ERCP for weak indications

11. Avoid solely diagnostic ERCP

12. Strongly consider MRCP as an alternative for diagnostic ERCP in low yield indications

13. Obtain informed, written consent that includes discussion of risks of fetal radiation

14. Perform ERCP at a hospital endoscopy unit rather than an ambulatory center in order to better manage procedural complications

15. Perform ERCP at a tertiary hospital rather than a community hospital where highly specialized consultants are likely to be present

16. Perform ERCP as expeditiously as possible to minimize radiation exposure and anesthesia medications

17. Employ modern and highly collimated radiation unit with the smallest possible field

18. Position patient as far as possible from radiation source consistent with reasonable images

19. If possible, employ “low-dose” radiation protocol in terms of kvp, field size, and frame rate

20. Place lead shield underneath patient between likely fetal area and radiation tube

21. Place dosimeters on patient above expected uterine location and record fluoroscopy time and total radiation dosage

22. Minimize procedure time, procure all anticipated endoscopy equipment within endoscopy room before beginning the procedure

23. Employ static images as opposed to continuous fluoroscopy to reduce radiation exposure

24. Use digital image acquisition technology if possible, instead of film-screen radiography

25. Position patient to permit anterior-posterior beam projection

26. Avoid image magnification

27. Employ last image-hold or fluoroscopy loop recording feature when possible rather than additional fluoroscopy

28. Consider radiation-free ERCP in conjunction with other techniques such as temporary stenting and, if needed, needle-knife and transpapillary sphincterotomy

29. Document ductal clearance without radiation using IDUS or choledochoscopy

30. X-ray image receptor should be placed as close as possible to the patient

31. Adjust patient position between choices of supine, prone, or lateral to minimize fetal radiation exposure

ERCP: Endoscopic retrograde cholangiopancreatography; kVp: Peak kilovoltage; IDUS: Intraductal ultrasound.

Table 3 Literature review of relatively large clinical studies on safety of endoscopic retrograde cholangiopancreatography during pregnancy

First author, yr, reference	Study characteristics	Findings
Tang SJ, 2009[39]	Large retrospective study of 68 ERCPs performed during 65 pregnancies.	Pancreatitis occurred in 11 pregnant patients (16%) after ERCP. No other major maternal complications occurred during pregnancy. No fetal deaths and no fetal malformations occurred. After ERCP 53 patients had deliveries at term (90% rate for known delivery outcomes). However, ERCP performed during first trimester had less favorable outcomes: preterm delivery = 20%, and low-birth-weight infants = 21%
Ludvigsson JF, 2017[42]	National cohort study in Sweden of 58 pregnant patients undergoing ERCP included in a much larger study of 3052 patients undergoing any gastrointestinal endoscopy during pregnancy.	Of 58 pregnant patients undergoing ERCP unfavorable fetal outcomes included: 3 (5.2%) preterm births, 0 (0%) stillbirths, 0 (0%) neonatal deaths, 12 (20.7%) Cesarean sections, 1 (1.7%) Apgar score < 7 at 5 min, 1 (1.7%) small for gestational age, and 3 (5.2%) with any major congenital malformation. All these pregnancy outcomes were similar to that of pregnancy outcomes for mothers not undergoing endoscopy during pregnancy
Jamidar PA, 1995[15]	Retrospective study of therapeutic ERCPs performed during 20 pregnancies.	Two significant complications: one spontaneous abortion 3 wk after ERCP, and 1 neonatal death 26 h. post-partum that occurred after the expectant mother underwent 3 therapeutic ERCPs during pregnancy with pancreatic stenting at each session complicated by post-ERCP pancreatitis. No other significant maternal or fetal complications
Gupta R, 2005[44]	Retrospective study of therapeutic ERCPs performed during 18 pregnancies for choledocholithiasis.	Complications: 1 mild postsphincterotomy bleed; and 1 mild pancreatitis and preterm labor after ERCP. All fetal outcomes were favorable. This study had long-term follow-up after intra-partum ERCP: all 18 infants had normal child development at 6 yr
Cappell MS, 2011[45]	Systematic literature review of 296 pregnant patients undergoing therapeutic ERCP including 254 (86%) in which fetal outcome was reported.	Fetal outcomes as reported in 254 cases included: healthy infants at birth in 237, prematurely born infants with low-birth-weight in 11, late spontaneous abortions in 3, infant death soon after birth in 2, and voluntary abortion in 1. Perinatal mortality was only about 1% despite pregnant mothers undergoing therapeutic ERCP mostly for major gallstone complications, such as obstructive jaundice, ascending cholangitis, or gallstone pancreatitis. No congenital anomalies were reported in the infants. These favorable data must be interpreted cautiously: in this literature review, fetal outcome data were missing in 42 (15%) of reported mothers undergoing ERCP during pregnancy

ERCP: Endoscopic retrograde cholangiopancreatography.

Table 4 Literature review of case series of radiation-free endoscopic retrograde cholangiopancreatography during pregnancy

First author, yr, reference	Number reported	Indications	Technique of radiation-free ERCP	Outcomes
Shah 2016[75]	Non-radiation ERCP attempted-31 non-pregnant subjects. 26 successfully underwent ERCP without fluoroscopy. 5 required fluoroscopy during ERCP	Adult patients with suspected biliary stones based on abnormal serum liver tests, abdominal imaging, and/or abdominal pain. Underwent EUS per protocol. Patients with suspected large stone burden, complicated stone disease, or difficult anatomy were excluded	Antecedent EUS used as a guide before ERCP. Selective cannulation confirmed by aspirating visible bile in 26 patients. 5 patients required radiation for double wire or precut papillotomy. All patients had EUS. 4 others had ERCP obviated by EUS	No adverse events among patients who underwent bile cannulation, sphincterotomy, and stone removal without fluoroscopy. One patient undergoing ERCP with fluoroscopy had moderated post-ERCP pancreatitis
Ersoz 2016[74]	22 patients: first trimester-2, second trimester-3, third trimester-17	Abdominal ultrasound demonstrates stone/sludge in gallbladder-22 (100%), choledocholithiasis-12, mean total bilirubin = 5.49 ± 1.66 mg/dL, acute cholangitis-2, acute cholecystitis-2	Selective biliary cannulation attempted with sphincterotome and confirmed by bile aspiration. Biliary sphincterotomy and balloon dilation-18/22 had visible gallstones, 3 required transpancreatic papillary septotomy	5 complications after ERCP: epigastric pain without elevated lipase elevation-2, mild pancreatitis treated conservatively-2, minor post-sphincterotomy bleeding successfully treated with epinephrine injection without blood transfusions. All delivered healthy infants at term
Sethi S, 2015[73]	3 patients: 14, 7, or 28 wk pregnant	1 and 2-Dilated CBD and total bilirubin > 5.0 mg/dL after laparoscopic cholecystectomy, 3-Dilated CBD, multiple gallstones and increased total bilirubin level	All cases: EUS-guided ERCP with selective biliary cannulation confirmed by bile aspiration. Biliary sphincterotomy and stone extraction(s) using balloon sweeps or Spyglass technology	Uncomplicated. All mothers did well-rapidly discharged from hospital. Fetal outcomes not reported
Agcaoglu O, 2013[72]	5 patients: mean gestational age = 20 wk, range 12-32 wk	Gallstone pancreatitis and obstructive jaundice-3, cholangitis and obstructive jaundice-2	Selective cannulation confirmed by aspiration or direct visualization of bile. After CBD cannulated guide-wire passed, sphincterotomy completed, and stones extracted by basket or balloon sweep	No maternal or fetal adverse events or short term complications. No long-term follow-up available
Yang J, 2013[71]	24 patients: first or second trimester-9, third trimester-15	All patients had severe biliary pancreatitis. Leukocyte count 15000-29000 × 106/L, serum amylase: 500-2000 units/L, increased bilirubin in 20	All patients underwent emergency ERCP without fluoroscopy and endoscopic biliary drainage. 15 patients in third trimester had pregnancy terminated: induced delivery-7, cesarean section-6, full-term normal delivery-2. Then underwent second ERCP with fluoroscopy to remove gallstones. 9 patients in early pregnancy underwent endoscopic retrograde biliary drainage in second ERCP without fluoroscopy. Had biliary stent for average of 3.8 mo	100% technical success rate: CBD stones removed in all 24 patients. Only 2 maternal complications: mild hemorrhage during second ERCP. All infants born healthy. At term births-20, premature births-4 with cesarean section (for severe intrauterine distress)
Huang P, 2017[70]	86 patients (largest series): no fluoroscopy-81 ultra-short duration of fluoroscopy-5. Mean gestational age = 22.5 wk, Range: 15-35 wk	Acute biliary pancreatitis-32, acute cholangitis-23, dilated CBD-20, severe nonbiliary acute pancreatitis-11	Underwent antecedent abdominal ultrasound or MRCP. CBD cannulated using a guide-wire and then catheter over guide-wire. CBD cannulation confirmed by aspiration or oozing of bile. Then endoscopic biliary sphincterotomy and endoscopic nasobiliary drainage or retrograde biliary drainage. 51 had biliary stents	Technical success: 81 without fluoroscopy.Complications in 8.1%:Biliary bleeding-2, acute cholecystitis-1, post-ERCP pancreatitis-2. All babies were healthy at up to 12 mo. follow-up. All babies had normal birth weights (> 3 kg). Mean Apgar score at 5 min = 9
Akcakaya A, 2009[69]	6 patients: mean gestational age = 23 wk, range: 14-34 wk	Choledocholithiasis-4, Cholangitis-1, Persistent biliary fistula after hydatid disease surgery-1 (undergoing 2 ERCPs)	All patients had biliary sphincterotomy and balloon sweeps. Precut sphincterotomy performed with needle-knife for 1 patient with impacted stone	Complete stone extraction confirmed by abdominal ultrasound. No post-ERCP complications, premature birth, abortion or intrauterine growth retardation were observed
Shelton J, 2008[68]	21 patients: first trimester-7, second trimester-9, third trimester-5	Jaundice and biliary colic-11, biliary pancreatitis-8, cholecystitis-1, abnormal intraoperative cholangiogram-1	Guide-wire inserted into CBD followed by sphincterotome over guide-wire. CBD cannulation then confirmed by suction of yellow bile via catheter in first 10 cases. In next 11 cases CBD cannulation confirmed by leakage of yellow bile around guide-wire. Then wire-guided biliary sphincterotomy performed followed by balloon sweeps to extract stones. Choledochoscopy used for bile duct clearance in 5 last cases	100% technical success without fluoroscopy. One case of moderate pancreatitis. All then became asymptomatic. Follow-up of 18 pregnancies: Uneventful delivery of healthy babies-17, premature delivery at 35 wk with low birth weight-1
Sharma SS, 2008[64]	11 patients: first trimester-2, second trimester-6, third trimester-3	Abdominal pain and jaundice-11, cholangitis-2, dilated CBD-11, gallstones-8	All had 2-stage procedures. First stage during pregnancy: biliary sphincterotomy and stenting without radiation, bile aspirated to confirm biliary cannulation. Second stage ERCP postpartum: Stents removed, cholangiogram performed. Stones removed by Dormia basket-8, mechanical lithotripsy-1, or open surgery-1, no residual stones-1	Marked symptomatic improvement after first stage of therapy. All had normal, full-term delivery. “Good” maternal and fetal outcomes

ERCP: Endoscopic retrograde cholangiopancreatography; EUS: Endoscopic ultrasound; CBD: Common bile duct; MRCP: Magnetic resonance cholangiopancreatography.